Fibroblasts derived from long-lived insulin receptor substrate 1 null mice are not resistant to multiple forms of stress

Reduced signalling through the insulin/insulin-like growth factor-1 signalling (IIS) pathway is a highly conserved lifespan determinant in model organisms. The precise mechanism underlying the effects of the IIS on lifespan and health is currently unclear, although cellular stress resistance may be important. We have previously demonstrated that mice globally lacking insulin receptor substrate 1 (Irs1−/−) are long-lived and enjoy a greater period of their life free from age-related pathology compared with wild-type (WT) controls. In this study, we show that primary dermal fibroblasts and primary myoblasts derived from Irs1−/− mice are no more resistant to a range of oxidant and nonoxidant chemical stressors than cells derived from WT mice

Toroidal black holes and topological censorship

Recent theorems regarding topological censorship are in apparent conflict with simulations of the collapse of rotating matter to form toroidal black holes. The geometry of a temporarily toroidal event horizon is analyzed and shown to be completely consistent with the theorems. A simple flat space model provides insight into the geometry of a toroidal black hole

Five minutes with Jeffrey C. Alexander: “Southern European countries are not just experiencing an economic crisis, but also an identity crisis”

Is there a ‘dark side’ to European modernity? As part of our ‘Thinkers on Europe’ series, EUROPP’s editors Stuart A Brown and Chris Gilson spoke to Jeffrey C. Alexander about his views on modernity, the European integration process, and the importance of cultural and political symbols to European democracy

Vitamin E-inspired multi-scale imaging agent

© 2018 Elsevier Ltd The production and use of multi-modal imaging agents is on the rise. The vast majority of these imaging agents are limited to a single length scale for the agent (e.g. tissues only), which is typically at the organ or tissue scale. This work explores the synthesis of such an imaging agent and discusses the applications of our vitamin E-inspired multi-modal and multi-length scale imaging agents TB-Toc ((S,E)-5,5-difluoro-7-(2-(5-((6-hydroxy-2,5,7,8-tetramethylchroman-2-yl) methyl) thiophen-2-yl) vinyl)-9-methyl-5H-dipyrrolo-[1,2-c:2’,1’-f][1,3,2]diazaborinin-4-ium-5-uide). We investigate the toxicity of TB-Toc along with the starting materials and lipid based delivery vehicle in mouse myoblasts and fibroblasts. Further we investigate the uptake of TB-Toc delivered to cultured cells in both solvent and liposomes. TB-Toc has low toxicity, and no change in cell viability was observed up to concentrations of 10 mM. TB-Toc shows time-dependent cellular uptake that is complete in about 30 min. This work is the first step in demonstrating our vitamin E derivatives are viable multi-modal and length scale diagnostic tools

Fiber-derived butyrate and the prevention of colon cancer

AbstractInhibition of the enzyme histone deacetylase by butyrate results in the direct transcriptional upregulation of the cyclin-dependent kinase inhibitor p21/Cip1/WAF1. We discuss a small-molecule-mediated signaling pathway to explain the suspected anti-colon-cancer properties of fiber-derived butyrate

Seismic radiation by magma injection: An anomalous seismic event near Tori Shima, Japan

The earthquake with a bodywave magnitude m_b=5.5, which occurred near Tori Shima, Japan, on June 13, 1984 (origin time: 0229:25.3 UT, 31.448°N, 140.036°E, depth of 10 km, m_b =5.5, M_S=5.5) is anomalous because it generated tsunamis which are disproportionately large for the magnitude of the earthquake. At Hachijo Island, 150 km from the epicenter, tsunamis were visually observed with peak-to-peak amplitude of 130 to 150 cm. Long-period seismic radiation is also anomalous. Love waves are almost absent, and Rayleigh waves are radiated with equal amplitude and phase in all directions. A simple double-couple model cannot explain these observations. With the assumption of no net volume change at the source, these data can be best explained with a compensated linear vector dipole (CLVD) with the principal tensional dipole in the vertical direction. The scalar moment of this dipole is 4×10^(24) dyn cm. Moment tensor inversions of long-period body waves and surface waves yield an almost identical solution. This CLVD source can be interpreted as horizontal fluid injection. The location of the event is in the Smith depression which is one of the nascent back arc basins just behind the Bonin arc. These basins are filled with thick sediments, and numerous young volcanoes are found near this site. Magmatic injection is most likely to occur in this tectonic environment. However, the time scale of the seismic event seems too short for magma injection to occur. A more likely mechanism involves water-magma interaction. The injection may be viewed as hydrofracturing driven by supercritical water heated by injected magma. The estimated volume of injected water is about 0.018 km^3 and that of basaltic magma is about 10% of this. This type of deformation is more efficient for tsunami generation than faulting with the same scalar moment

Computational Study of an Axisymmetric Dual Throat Fluidic Thrust Vectoring Nozzle for a Supersonic Aircraft Application

A computational investigation of an axisymmetric Dual Throat Nozzle concept has been conducted. This fluidic thrust-vectoring nozzle was designed with a recessed cavity to enhance the throat shifting technique for improved thrust vectoring. The structured-grid, unsteady Reynolds- Averaged Navier-Stokes flow solver PAB3D was used to guide the nozzle design and analyze performance. Nozzle design variables included extent of circumferential injection, cavity divergence angle, cavity length, and cavity convergence angle. Internal nozzle performance (wind-off conditions) and thrust vector angles were computed for several configurations over a range of nozzle pressure ratios from 1.89 to 10, with the fluidic injection flow rate equal to zero and up to 4 percent of the primary flow rate. The effect of a variable expansion ratio on nozzle performance over a range of freestream Mach numbers up to 2 was investigated. Results indicated that a 60 circumferential injection was a good compromise between large thrust vector angles and efficient internal nozzle performance. A cavity divergence angle greater than 10 was detrimental to thrust vector angle. Shortening the cavity length improved internal nozzle performance with a small penalty to thrust vector angle. Contrary to expectations, a variable expansion ratio did not improve thrust efficiency at the flight conditions investigated

Generation of Inhomogeneous Acoustic Waves Using an Array of Loudspeakers

In previous studies it has been shown that pressure fields created by inhomogeneous sound waves (waves which decay in a direction perpendicular to their propagation direction) are able to transmit energy into objects more effectively than ones created by conventional sound waves. This behavior may be useful in the detection of hidden explosive threats. To explore this, a device capable of constructing inhomogeneous waves is being developed. The proposed device is an acoustic array consisting of several high-frequency speakers. The speakers are independently driven to construct a desired inhomogeneous pressure field on a target surface. Inhomogeneous pressure fields were reconstructed across a span of decay parameters and standoff distances. Results show low root-mean-square errors at realistic levels of power consumption. These results imply that the device can recreate desired inhomogeneous pressure fields with high enough accuracy and low enough power consumption to test the energy transmission properties of inhomogeneous waves on mock explosives, which may be useful in applications related to improvised explosive device detection and defeat